Renal diseases include inflammatory renal diseases such as nephritic syndrome, nephrotic syndrome and the like, angiopathic diseases such as atheroembolic renal disease, renal vein thrombosis and the like, diabetic nephropathy caused by diabetes and the like. In patients with such renal diseases, nutritional deficiency, i.e., malnutrition, is often found, and malnutrition is an important factor that influences the prognosis of patients with renal diseases. In addition, when kidney function decreases due to the aforementioned diseases, shortage of blood flow into the kidney due to hemorrhage, cardiac failure and the like, urinary tract obstruction due to prostatic hyperplasia and the like, kidney damage and the like, acute or chronic renal failure is developed, sometimes requiring artificial dialysis to sustain life. Among the dialysis-introduced patients, a condition called MIA syndrome wherein malnutrition, chronic inflammation and arteriosclerosis are related to each other to exert an adverse influence has been a problem. Furthermore, when the blood C-reactive protein (CRP) concentration, which is one of the indices of inflammation, is not less than 0.2 mg/dL on dialysis introduction, the risk of death is reported to increase when the value is higher (non-patent document 1). Currently, however, an appropriate treatment method for these patients has not been established, and the patients are dealt with by performance of an optimal dialysis for each patient, determination of an optimal amount of dialysis, and removal of endotoxin in dialysates.
The above-mentioned malnutrition of patients with renal diseases is preferably dealt with by improvement with nutrition supplements. However, when inflammation persists, normal nutrition supplementation is not expected to provide a sufficient improvement effect, since various biological reactions occur such as reduction in appetite, degradation of body protein, increase of protein catabolism, decrease of protein anabolism, hypermetabolism due to cytokine and the like.
As a medical preparation for patients with renal diseases, a preparation containing reduced amounts of protein, phosphorus, potassium, sodium and water as compared to general-purpose liquid foods has been used heretofore. As an amino acid preparation for renal failure, moreover, “Amiyu® granule”, “Neoamiyu®” and the like containing a higher amount of essential amino acid (manufactured by Ajinomoto Pharma Co., Inc.) are commercially available. However, the products do not contain lipid, which is an important nutrient for energy supplementation and suppression of inflammation, and these medical preparations have not shown a clear improvement of inflammation.
On the other hand, a report has documented that, in a pilot test by dialysis patients, the blood CRP concentration decreased by administration of a fish oil capsule containing 427 mg of eicosapentaenoic acid and 244 mg of docosahexaenoic acid for 12 weeks (non-patent document 2). However, since the aforementioned fish oil capsule does not contain protein, it does not improve malnutrition. It has also been reported that administration of 1.2 g of ω-3 fatty acid to 11 dialysis patients for 12 weeks did not decrease CRP and did not improve nutrition condition (non-patent document 3). Furthermore, since ω-3 fatty acid such as eicosapentaenoic acid and the like has a problematic taste, it needs to be considered that addition in a high concentration is poor compliance, and may cause a bleeding tendency due to it's platelet aggregation suppressive action. With ω-3 fatty acid alone, therefore, inflammation suppressive and malnutrition improving effects in dialysis patients cannot be expected, which suggests the need for use in combination with other nutrients.
When a nutrition composition with a ratio of ω-6 fatty acid/ω-3 fatty acid in fatty acid of 1.6 was administered for 4 weeks to dialysis patients associated by malnutrition and inflammation, a significant decrease in CRP or increase in body weight was not found (non-patent document 4). The content of protein in the composition described in this document is as high as 3.8 g/100 kcal, which prevents easy application thereof to patients under restriction of protein intake. Furthermore, since the aforementioned composition does not contain free amino acid, and shows low selenium and zinc contents, the importance thereof is also suggested.
On the contrary, patent document 1 discloses a nutrition composition containing protein, fat, carbohydrate, vitamin, mineral and L-arginine. However, when nitric oxide (NO) is produced in excess by L-arginine, hypotension may be induced. Thus, a long-term administration of this nutrition composition requires attention. Moreover, patent document 2 discloses a composition for patients with cachexia and/or anorexia, which contains a mixed oil with a weight ratio of ω-6 fatty acid to ω-3 fatty acid of 0.1-3.0, amino acid containing branched chain amino acid, and antioxidant such as β-carotene, vitamin C, vitamin E, selenium and the like. Different from healthy individual, however, patients with renal diseases are feared to develop side effects due to the administration of large amounts of vitamin A and vitamin C. These contents of the composition are not suitable for patients with renal diseases.
For renal diseases showing malnutrition such as hypoproteinemia and the like, a nutrition composition with an attention to protein supplementation is desired. Non-patent document 5 discloses that, by ingestion of a soybean protein, glomerular filtration rate of the kidney, renal plasma flow and fractional clearance of albumin decrease, and renal vasodilator action, which is observed with ingestion of animal-derived protein, is eliminated, thus suggesting a less load applied by soybean protein on the kidney.
The present Applicant already found usefulness of branched chain amino acid, and disclosed a life prognosis-improving agent for patients with renal diseases, which contains branched chain amino acid (patent document 3). With regard to histidine, which has been considered an essential amino acid in renal diseases from long ago and is known to show an antioxidant action, the plasma histidine concentration of patients with chronic renal diseases has been shown to significantly decrease (non-patent document 6). However, they do not consider lipid, and branched chain amino acid or histidine, and a lipid containing ω-3 fatty acid and ω-6 fatty acid at a particular weight ratio, and further, a soybean protein have not been used in combination.
As one of the causes of arteriosclerosis, which is one pathology of MIA syndromes, low-density lipoprotein (LDL) peroxide produced by denaturation of LDL cholesterol due to an oxidative stress is known, and an antioxidant substance is important for the improvement of MIA syndromes. Therefore, patients with renal diseases who show MIA syndrome, and abnormal lipid metabolism such as high LDL-cholesterolemia and the like desire a nutrition composition with consideration of the above-mentioned substance, factors and the like. However, such composition has not been known to date.